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CALVADORES, CHLOE IANNAH E.

JANUARY 8, 2021
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DUA LIPID: What’s cooking, good looking viewers? Welcome DUA LIPID: We’re currently here at the FAT building
back to our channel! First off, we would like to greet each and and right now we’re heading to the Beta Oxidation
everyone of you, our very loyal viewers, a HAPPY HAPPY new department at level mitochondria.
year! We hope ya’ll were able to indulge in all the good food
with your families over the holidays! Now that the festivities are
over, it’s time to return to hustle mode! In today’s episode, we
will do part 2 of our office tour at the Charles and Keith-o
Corporation! How are you today, Proteina?

PROTEINA TURNER: Not gonna lie, I’m still very much stuffed
from all the treats I had over the break, Dua! I’m pretty sure you
are too, haha! I’m honestly so excited for today’s episode
because we will be touring you guys around the FAT building,
where you guys will meet more of our office friends! So without
further ado, let’s get started!
CALVADORES, CHLOE IANNAH E. JANUARY 8, 2021
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PROTEINA TURNER: With us today is our big boss, 
 DUA LIPID: By the way, Ms. FATTYricia is actually the
Ms. FATTYricia!
head of all the departments in the FAT building. Can
you tour us around, FATTYricia?

FATTYRICIA: Hey there! Nice to meet you!

FATTYRICIA: Oh yes, I would love to!

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FATTYRICIA: As you guys may have heard, our FATTYRICIA: Before we start, I would just like to
carbohydrate supply in the company is at an all time emphasize that before fatty acids can be utilized for
low. But that’s not a problem because we have a lot energy, they need to be converted to an active
of stored fat! When the carbohydrate supply is limited intermediate first. And that’s one of the things we do
or extinguished, the company relies on glycogen for here at the Beta Oxidation department. The first
energy. But since that is also limited, we need fats to station is located at level cytosol while the rest are
help us sustain our operations. Here in the FAT located at level mitochondria.
building, we manufacture fats to be able to produce
energy to keep our company going!
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FATTYRICIA: In the first station, free fatty acids are FATTYRICIA: In the same station, the inorganic
converted to Acyl CoA by my good friend, HAZEL phosphate is hydrolyzed by another coworker, Mr.
CoA Synthetase (acyl coA synthetase)! In the Organic PyrophosPATase (organic pyrophosphatase).
presence of ATP and CoA, Ms. HAZEL CoA With the loss of high energy phosphate, he ensures
Synthetase makes use of a high energy phosphate to that the job goes to completion.
catalyze the conversion of fatty acids to active fatty
acids or Acyl CoA. In the process, ATP and inorganic
phosphate are produced.
CALVADORES, CHLOE IANNAH E. JANUARY 8, 2021
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FATTYRICIA: In this next one, Acyl CoA is FATTYRICIA: We now proceed to the real deal,
transported from level cytosol to level mitochondria which is Beta Oxidation! Beta Oxidation constitutes
and brought to this station. My hardworking friend, the bulk of what we do here in the department. This
KARENitine (carnitine shuttle), transports Acyl CoA, station is where the first dehydrogenation happens!
which is a very large and polar molecule, to the inner Ms. aCHELLE-CoA dehydrogenase (acyl CoA
mitochondrial level. Her job is very crucial because dehydrogenase) removes the two hydrogen atoms
the movement from cytosol to mitochondria is from Acyl CoA, with the help of her co-worker,
necessary for the whole reaction to proceed. flALVIN adenine dinucleotide, also known as FAD.
The end products are Δ2-trans-enoyl-CoA and
FADH2, which will be used in the next station. This
whole process yields 1.5 ATPs.
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FATTYRICIA: Let’s move on! I want you to meet my FATTYRICIA: Are you ready for more?!?! Let’s go
good friend, Δ2-enoyl-CoA hydraTESS (Δ2-enoyl-CoA check out the next station! In this station, dehydration
hydratase)! In this next station, water is added to Δ2- of 3-hydroxyacyl-CoA occurs. My lovely friend over
trans-enoyl-CoA to saturate the double bond and here, 3-hydroxyacyl-CoA dehydroJANICE (3-
form 3-hydroxyacyl-CoA. My friend, Δ2-enoyl-CoA hydroxyacyl-CoA dehydrogenase), together with her
hydraTESS, is in charge of this! co-worker, nicoTINAmide adenine dinucleotide or Ms.
NAD+ catalyzes this dehydrogenation reaction to yield
3-ketoacyl-CoA and NADH+. This dehydrogenation
reaction yields 2.5 ATPs.
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FATTYRICIA: Finally, in this last station we have the THIOLAYS: Oh, by the way! I want you to meet my
very handsome Mr. thioLAYS! Yes, just like the potato co-worker, co-ASH! He helps me accomplish my task
chips! So, can you tell us about your job, sir?
in this station. Say hi, co-ASH!

THIOLAYS: Yes, of course! Hey guys, I’m thioLAYS COASH: Hey there! nASH to meet you!
and I am in charge of the thiolytic cleavage of 3-
ketoacyl-CoA. Basically, 3-ketoacyl-CoA is split at
the 2,3 position by no other than myself, generating
acetyl CoA and a new acetyl CoA that is two carbons
shorter than the original one.

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FATTYRICIA: That’s it for our Beta Oxidation DUA LIPID: I had so much fun going around,
department tour! What do you think? FATTYricia! How about you Proteina?

PROTEINA TURNER: I had the best time and I’m


pretty sure our viewers loved it too! Anything else
you wanna say FATTYricia before we move on to the
next one?
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FATTYRICIA: Oh right! I'm sorry, I almost forgot! I’d FATTYRICIA: Long chain fatty acids, with 12-20 carbon atoms,
like to introduce some more of my co-workers! As I’e are the most common and the only ones that require
said, in the Beta Oxidation department, we messengers to go to the inner mitochondrial level. That’s why
manufacture fatty acids. You see, these fatty acids KARENitine’s job is very important! The other types just diffuse
vary in their chain lengths and each of them, in their to the mitochondrial membrane, like magic! These include:
respective stations, is catalyzed by different medium chain FAs, with 4-12 carbon atoms, which are
employees as well. Let me introduce them one by catalyzed by MIMIdium chain Acyl-CoA dehydrogenase, short
one. chain FAs, with 2-4 carbon atoms, are catalyzed by SHARt
chain Acyl-CoA dehydrogenase, and long chain FAs, as I’ve
mentioned are catalyzed by long SHANE Acyl-CoA
dehydrogenase! Very long chain FAs, with more than 20 carbon
atoms, which are catalyzed by veREY long chain Acyl-CoA
dehydrogenase, are transported to the peroxisome level by a
special messenger, but we will reveal him some other time! Say
hi to our viewers, everyone!
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FATTYRICIA: That’s it! Hope to see you guys again DUA LIPID: This next department is very special. You
soon!
will meet them in a little while but I’ll just give a little
background about the department and why it’s so
PROTEINA TURNER: Thank you so much for that important. Here at the Charles and Keith-o
very informative tour, FATTYricia!
Corporation, we specialize in the manufacture of
ketone bodies. This next department is basically the
DUA LIPID: Are you guys ready to meet the next core of the whole company.

department?
PROTEINA TURNER: Ketone bodies? What are
thooooose?!

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DUA LIPID: Ketone bodies are exported to the brain PROTEINA TURNER: I want you all to meet Mr.
office because they use these ketone bodies to QUITOne! He is in charge of the Ketogenic
operate when the carbohydrate supply is very very department. Introduce yourself, my friend.

low. In the company, we have generous amounts of


fatty acids. However, the brain cannot utilize them. It QUITONE: Hey guys! I am QUITOne (ketone) and I
prefers ketone bodies. The brain is very important will be touring you around the Ketogenic department.
since they send out commands to essentially every I hope you all are as excited as I am!
department in the company. Without it, the
corporation cannot function. Okay, enough of the
talking! Let me introduce another special guest who
will tour us around the most exciting department in
the company! Are you guys ready???
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QUITONE: Okay so I’d like to start off with a very brief


QUITONE: So that’s how ketone bodies are formed!
overview of how ketone bodies are formed. Acetyl CoA is
Quite a lot to take in but pretty interesting, right? Let’s
crucial in the production of ketone bodies. Acetyl coA is acted
now move on to the stations for a much more detailed
upon by my friend, KAYEtothiolase (ketothiolase), and
rundown of our work here at the department! The
coverted to acetoacetyl CoA, which is then converted to HMG
stations here are divided into two: those that specialize
CoA. HMG CoA is acted upon by another co-worker, Ms.
in the biosynthesis of ketone bodies and those that are
HMG-CoA LYAse (HMG CoA lyase) to form acetoacetate and
in charge of the breakdown of ketone bodies. You’ll
a c e t y l C o A . F i n a l l y, a c e t o a c e t a t e f o r m s b o t h β -
learn more about them as we go along but let’s start
hydroxybutyrate and acetone and this reaction is catalyzed by
with biosynthesis!
no other than, Ms. BETHa-hydroxybutyrate dehydrogenase
(β-hydroxybutyrate dehydrogenase)! Here in our corporation,
as you may already know, the carbohydrate supply is very
low, but as my co-workers have mentioned, we take in A LOT
of fat. Because of this, there is an increased synthesis of
acetoacetate.
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QUITONE: In this first station, Acetyl CoA is QUITONE: Alright, let’s move on! In this next
converted to Acetoacetyl CoA by this beautiful lad station, Acetoacetyl CoA is then converted to
right here. Say hi, β-KAYEtothiolase (β-ketothiolase)! HMG CoA by HMG CoA syntheTRACE (HMG CoA
One CoA is removed from Acetyl CoA to produce synthetase)! Here, acetyl CoA condenses with
Acetoacetyl CoA. If you guys remember the thiolase acetoacetyl CoA, and CoA is removed to produce
station in the Beta Oxidation department, this station HMG CoA! Pretty cool, huh?
right here is the reverse of that one! Interesting, right?
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QUITONE: Moving on, in this last station, HMG CoA QUITONE: Can you tell us more about your station,
is converted to acetoacetate by the very hardworking, HMG CoA LYAse?

Ms. HMG CoA LYAse (HMG CoA lyase)! In this


process, acetyl CoA is also produced. Say hi to our HMG COA LYASE: Sure! Actually, acetoacetate that
viewers! is produced in this station has three fates. First, it can
directly be brought to the extrahepatic tissue office, at
the level mitochondria, for production of energy via
oxidation. It can also be reduced by Mr. NAD-
depenDANt dehydrogenase (NAD-dependent
dehydrogenase) to β-hydroxybutyrate, which can be
transported to the inner mitochondrial level to be
used as fuel for other departments. Lastly, it can
undergo spontaneous decarboxylation, which
releases CO2, generating acetone, and is used to
produce D-3-hydroxybutyrate. Very versatile!
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QUITONE: Okay moving on, in ketolysis, only two QUITONE: In the next and final one, the cleavage of
stations are involved. Let’s go ahead and meet more an acetyl group from acetoacetyl CoA to form acetyl
friends! The first station involves the reconstitution of CoA is performed by my great friend, Mr. MAT! What’s
acetoacetyl CoA from acetyl CoA by Mr. succiNEIL up, Mr. MAT?

CoA oxoacid transferase (succinyl CoA oxyacid


transferase), or you can call him SCOT. Say hello, sir! MAT: Hi! I’m Methylacetoacetyl CoA thiolase, MAT for
short!
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QUITONE: So, that concludes today’s tour at the PROTEINA TURNER: Thank you so much, QUITOne,
Ketogenic department. What do you guys think?
for touring us around! That was a tiring one but I HAD
SO MUCH FUN!

DUA LIPID: Honestly, you guys seem so busy! But


I’m sure you have so much fun working around here. QUITONE: My pleasure! I’ll see you guys around!

Everyone is so friendly and very hardworking!

PROTEINA TURNER: I couldn’t agree more, Dua!

* note: continued on Chapter 3: Integration

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